On the issue of diagnostic value of determining the level of receptors and their ligands in blood in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) occupies the first place in the structure of mortality due to oncological diseases. Late diagnosis worsens the effectiveness of its treatment. There are no informative biomarkers that allow us to judge the prevalence of the tumor process, especially in the early stages of NSCLC. To determine the level of CXCL5, CXCL8, CXCR1 and CXCR2 in the peripheral blood of patients with NSCLC to assess the possibility of their use in the diagnosis of the disease. The material was the blood of 218 patients with NSCLC, 19 patients with lung hamartoma and 42 healthy people. The concentration of CXCL5, CXCL8, and SCC in blood serum was determined by enzyme immunoassay, the CYFRA 21-1 level was determined by immunochemiluminescence analysis. The proportion of leukocytes equipped with CXCR1 and CXCR2 receptors and the fluorescence intensity of receptor complexes with antibodies (MFI) in them were measured by flow cytometry. MFI CXCR1 in granulocytes and the proportion of lymphocytes supplied CXCR2, increased in the blood already at stage I of NSCLC and showed an even more significant increase in subsequent stages. The level of these indicators was correlatively related to the stages and characteristics of NSCLC. Measuring the level of MFI CXCR1 in the blood serum makes it possible to diagnose the early stages of NSCLC with a sensitivity of 87.4% (specificity - 73.8%). Determination of the proportion of lymphocytes equipped with CXCR2 demonstrates comparable diagnostic sensitivity (87.2%) and specificity of 66.7% in the detection of stages I-II of NSCLC. MFI CXCR1 in granulocytes can also be used to differentiate stages I and II of NSCLC (diagnostic sensitivity - 75,3%, specificity - 69,6%). The sensitivity of determining for this purpose the proportion of lymphocytes equipped with CXCR2 is 75.0% with a specificity of 71.7%. In 89.7% of patients with stages III-IV NSCLC, the MFI CXCR1 in granulocytes exceeds the threshold value of 47.8 (specificity - 74.8%). Diagnostic sensitivity of determining the proportion of lymphocytes for this purpose was 90.7%.

Preoperative blood markers for prediction of recurrence-free survival after surgical treatment of patients with stage III lung adenocarcinoma.

The possibility of the preoperative level of 42 indicators characterizing the cellular composition and metabolism in blood of patients with stage III lung adenocarcinoma (AC) to predict their relapse-free survival was studied. Blood samples of 451 patients with newly diagnosed AK stage III after their surgical treatment (resection volume - R0) have been investigated. The duration of the relapse-free period (period of observation - 1 year), cellular composition of the blood, concentration of C-RP, albumin, Cyfra 21-1 antigens, SCC, TPA, chemokines CXCL5, CXCL8, pyruvate kinase TuM2 PK isoenzyme, HIF-1α and hyaluronic acid in blood serum so as the proportion of blood cells with CXCR1 and CXCR2, CD44V6 receptors in blood serum were measured. To determine the dependence of the duration of the relapse-free period after the treatment on the observation time, Kaplan-Meier graphs were built. The relationship between the determined parameters and survival was judged using single- and multi-factor Cox proportional hazard models. Comparison of groups with different risk of AK recurrence was performed using the Log Rank test and χ2. The assessment of the predictive information content of laboratory tests was carried out using ROC analysis. It was shown that the concentration of monocytes, eosinophilic leukocytes, the relative quantity of lymphocytes with CXCR1 receptor, the level of Cyfra 21-1 before surgical treatment were associated with the duration of the relapse-free period. A regression equation was compiled, which included the level of Cyfra 21-1, relative content of lymphocytes with CXCR1, and the eosinophilic leukocytes / monocytes ratio. Based on the threshold value Y=0,597, a Kaplan-Meier plot of patient survival was built and the results of it correspond to the TNM stratification. The prognostic sensitivity of the results of the equation - 85,7%, the specificity - 94,7%.

[Predicting the risk of tumor progression in patients with early stages of adenocarcinoma and squamous cell lung carcinoma based on laboratory parameters]. / Prognozirovanie riska opukholevoi progressii u patsientov s rannimi stadiiami adenokartsinomy i ploskokletochnogo raka legkogo na osnove laboratornykh pokazatelei.

Non-small cell carcinoma (NSCLC) prevails in the structure of the incidence of lung cancer. In patients with I stage NSCLC, only 60-70% overcome the 5-year survival barrier, and at II stage it decreases to 35-40%. The reason for such a high mortality rate is almost always a relapse of the disease. The main histological forms of NSCLC - adenocarcinoma (AC) and squamous cell carcinoma (SCLC) - differ in the course, protocols and effectiveness of the treatment. Comparative survival data for AK and PCLC are controversial, and reliable biomarkers for determining the risk of tumor progression are lacking. In thus study we have investigated the possibility of using laboratory parameters characterizing the level of some blood proteins involved in carcinogenesis in patients with early stages of AC and SCLC to determine the risk of disease progression. We retrospectively analyzed the duration of the relapse-free period after surgical treatment for one year in 1250 patients (816 with stages I and II of adenocarcinoma, G1-3 and 434 with early stages of SCLC, G1-3). In 81 patients with AC and 36 - with SCLC (stages I-II, G1-3) the level of CYFRA 21-1 and SCC by electrochemiluminescent method, chemokines CXCL5, CXCL8, TPA, pyruvate kinase M2, HIF-1α and hyaluronic acid by enzyme immunoassay, receptors CXCR1, CXCR2, CD44v6 by flow cytometry were determined. Using the Kaplan-Meier graphical analysis, groups of low (stage I G1-2 + stage II G1) and high (stage I G3 + stage II G2-3) risk of tumor progression were identified. In the case of the one-year survival rate of patients with AC was higher than with SCLC. In patients with AC and a high risk of tumor recurrence, compared with a low one, the level of CYFRA 21-1, the mean intensity of fluorescence (MFI) of the CXCR1 receptor in granulocytes, and the relative content of the CXCR2 receptor in lymphocytes were higher. In the case of rapid progression of SCLC in patients, the relative content of the CXCR2 receptor in lymphocytes, the proportion of monocytes equipped with the CD44v6 receptor, and the SCC level were higher than with slow progression. Regression equations, including combinations of the above parameters (threshold value for AC - 0,512, for SCLC - 0,409, sensitivity - 91,9% and 90,0%, specificity - 90,0% and 87,5%, respectively), allow to predict the probability of tumor recurrence.

[Diagnostic efficiency of determining CXCR1, CXCR2 and hyaluronic acid blood level in non-small cell lung cancer patients]. / Diagnosticheskaia éffektivnost' opredeleniia urovnia retseptorov CXCR1, CXCR2 i gialuronovoi kisloty v krovi pri nemelkokletochnom rake legkogo.

In the structure of lung cancer incidence most cases belong to non-small cell lung cancer (NSCLC) which is subdivided into two histological subtypes: adenocarcinoma (AC) and squamous cell carcinoma (SCC). A five-year survival rate of patients with stage I NSCLC is two times higher than in patients with stage II and more than five times higher than in stages III-IV. Currently, there are no informative blood biomarkers to diagnose early stages of NSCLC. The aim of the study was to evaluate complex determination of hyaluronic acid (HA), CXCR2 and CXCR1 levels blood of patients with AC and SCC. Blood samples from of 107 patients with SCC, 90 patients with AC, and 40 healthy people were used in this study. Concentration of HA in blood serum was determined by enzyme linked immunoassay. The level of CXCR2 and CXCR1 was determined by flow cytometry. Diagnostic parameters were determined by constructing mathematical models in the form of regression equations using the method of stepwise inclusion of predictors and subsequent ROC-analysis. Results of the study indicate that MFI CXCR1 in granulocytes, proportion of lymphocytes containing CXCR2 and concentration of HA in blood serum in stage I AC and SCC are significantly higher than in healthy people. The level of these parameter significantly increases at stage II of the disease compared to stage I and demonstrates further growth at its later stages. Based on the obtained results, regression equations were created: (i) including MFI CXCR1 in granulocytes, proportion of lymphocytes supplied with CXCR2 and HA concentration in the serum to detect stages I-II SCC (diagnostic sensitivity - 95.7%, specificity - 93.7%, threshold value - 0.59) and stages III-IV SCC (diagnostic sensitivity - 93.1%, specificity - 93.3%, threshold value - 0.64); (ii) including the proportion of lymphocytes supplied with CXCR2 MFI CXCR1 in granulocytes and CYFRA 21-1 blood level, which allows the detection of I-II stages of AC (sensitivity - 91.3%, specificity - 94.7%, threshold value - 0.61); (iii) including the proportion of lymphocytes supplied with CXCR2 and CYFRA 21-1 blood level, which allows the detection of AC stages III-IV (sensitivity - 94.6%, specificity - 91.3%, threshold value - 0.15); (iv) including the proportion of lymphocytes supplied with CXCR2 and HA level in the serum to differentiate stage II SCC from stage I (sensitivity - 94.4%, specificity - 87.5%, threshold value - 0.44) and II stage AC from stage I (sensitivity - 88.5%, specificity - 91.2%, threshold value - 0.46).